Gao Xiaoqiang, Jia Xiaodong, Xu Moyan, Xiang Jiao, Lei Jin, Li Yinyin, Lu Yinying, Zuo Shi
Department of Hepatobiliary Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Department of Liver Disease, Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.
Front Oncol. 2022 Jun 24;12:879810. doi: 10.3389/fonc.2022.879810. eCollection 2022.
Gamma-aminobutyric acid transaminase (ABAT) catalyzes the conversion of gamma-aminobutyric acid (GABA) into succinic semialdehyde. Although some evidence supports a key role of ABAT in the progression of hepatocellular carcinoma (HCC), no systematic analysis is available. Thus, this study aimed to investigate the possible mechanisms related to low ABAT expression and the prognostic value and potential functions of ABAT in HCC.
We obtained relevant datasets from the Encyclopedia of RNA Interactomes, MethSurv, cBioPortal, TISIDB and The Cancer Genome Atlas and used bioinformatic methods to analyze DNA methylation, copy number variation, gene mutation, and upstream microRNAs (miRNAs) of ABAT, exploring the potential relationship between ABAT expression and the prognosis, glycolysis, and immune infiltration in HCC.
The results indicated that ABAT expression was lower in HCC tumor tissues than in normal tissues or adjacent tissues. Low ABAT expression was related to patient age, T stage classification, pathologic stage, histological grade, and alpha-fetoprotein level of HCC. Kaplan-Meier survival analyses indicated that low ABAT expression was correlated with poor HCC prognosis. ABAT was also verified as an independent risk factor in HCC Cox multivariate analysis. Gene set enrichment analysis showed enrichment in various signaling pathways. Furthermore, DNA methylation, copy number variation, and gene mutation potentially induced low ABAT expression; miR-135a-5p was a potential upstream miRNA of ABAT. Additionally, ABAT expression was associated with glycolysis-related genes, infiltrated immune cells, immunoinhibitors, and immunostimulators in HCC.
Our study reveals that deficient ABAT expression is correlated with disease progression and poor prognosis in HCC because of its role in tumorigenesis and tumor immunity.
γ-氨基丁酸转氨酶（ABAT）催化γ-氨基丁酸（GABA）转化为琥珀酸半醛。尽管有一些证据支持ABAT在肝细胞癌（HCC）进展中起关键作用，但尚无系统分析。因此，本研究旨在探讨与ABAT低表达相关的可能机制以及ABAT在HCC中的预后价值和潜在功能。
我们从RNA相互作用组百科全书、MethSurv、cBioPortal、TISIDB和癌症基因组图谱中获取相关数据集，并使用生物信息学方法分析ABAT的DNA甲基化、拷贝数变异、基因突变和上游微小RNA（miRNA），探索ABAT表达与HCC预后、糖酵解和免疫浸润之间的潜在关系。
结果表明，HCC肿瘤组织中ABAT表达低于正常组织或癌旁组织。ABAT低表达与HCC患者的年龄、T分期、病理分期、组织学分级和甲胎蛋白水平有关。Kaplan-Meier生存分析表明，ABAT低表达与HCC预后不良相关。在HCC的Cox多因素分析中，ABAT也被证实为独立危险因素。基因集富集分析显示在各种信号通路中富集。此外，DNA甲基化、拷贝数变异和基因突变可能诱导ABAT低表达；miR-135a-5p是ABAT的潜在上游miRNA。此外，ABAT表达与HCC中的糖酵解相关基因、浸润免疫细胞、免疫抑制剂和免疫刺激剂有关。
我们的研究表明，ABAT表达缺陷与HCC的疾病进展和不良预后相关，因为它在肿瘤发生和肿瘤免疫中起作用。
